Risk of visual impairment which includes Age-Related Macular Degeneration (AMD) and cataracts increases as the average person ages. This can be due to changes in the structure and function of the eye itself as well as changes that can affect the functionality of the structures in the central nervous system that support visual perception. Dagnelie G. (2013). Age-related psychophysical changes and low vision. Invest Ophthalmol Vis Sci, 54(14): ORSF88-93.
The Age Related Eye Disease Study (AREDS) is a long-term multicenter study that has investigated the natural progression of AMD and its improvement with supplementation. The AREDS study group tested variations of formulations and determined the most effective formulation to contain lutein, zeaxanthin, copper, zinc, vitamin C, and vitamin E. A variety of zinc levels did not alter the effectiveness. Prior to the present invention, the AREDS studies, and supplements arising therefrom, were done using supplementation that required the participant to swallow an oral dosage form. However, the population that would benefit the most from an eye health related supplement would also be at a higher risk of dysphagia, which is a common issue as people age.
Two of the more severe visual impairments that can occur are Age-Related Macular Degeneration (AMD) and cataracts. AMD is an incurable disease characterized by drusen, retinal pigment epithelial abnormalities, geographic atrophy, retinal pigment epithelial detachment, choroidal neovascularization and disciform scarring. Age-Related Eye Disease Study Research Group. (1999). The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1. Control Clin Trials, 20(6): 573-600.
AMD is the leading cause of blindness in the developed world and the number of people with advanced AMD is expected to double over the next twenty (20) years, while cataracts are opacities in a lens which is normally transparent. The most common type of cataract is age-related and is the leading cause of visual impairment and blindness in the United States of America (USA).
In 1999, the Age-Related Eye Disease Study (AREDS) was conceived as a long-term multicenter study of the natural progression of AMD. The study spanned eleven (11) clinical centers across the USA and was sponsored by the National Eye Institute. The AREDS study included a randomized clinical trial involving 4757 participants aged 55-80 years, which was designed to evaluate the effect of a high dose supplement of antioxidant vitamins and minerals on the progression of AMD and cataract. At the time of the first AREDS study, there was an absence of clinical studies with definitive results on the safety and efficacy of pharmacologic doses of vitamins and minerals to treat these two particular eye conditions. Due to extensive marketing, the general public, however, still sought these formulations in order to self-medicate their conditions. Therefore, the AREDS study was conducted to provide descriptive data on the clinical course of AMD and cataract, attempt to identify factors that influence their development and progression, as well as evaluate the potential efficacy of an antioxidant rich vitamin and mineral formulation.
The formulation evaluated by the AREDS researchers contained five hundred (500) mg of vitamin C, four hundred (400) IU of vitamin E, fifteen (15) mg of beta-carotene, eighty (80) mg of zinc, and two (2) mg of copper; copper was added to the formulations containing zinc to prevent deficiency. The chosen formulation was based on recommendations from expert nutritionists, ophthalmologists and biochemists who reviewed existing science and epidemiological data. The benefits of supplementation with this combination of vitamins and minerals was observed in people who began the study at high risk for developing advanced AMD, those with intermediate AMD, and those with advanced AMD in one eye only. Those taking the supplement for five years had a reduced risk of developing advanced stages of AMD and its accompanying visual loss over the supplementation period by twenty-five (25) percent. This was the first clinical study to examine people at high risk for developing advanced AMD. The first AREDS study showed that slowing the progression of AMD could save the vision of those at risk of impairment. Age-Related Eye Disease Study Research Group. (2001). A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss: AREDS Report No. 8. Arch Ophthalmol, 119: 1417-36.
The Age-Related Eye Disease Study 2 (AREDS2) was conducted to assess whether the formulation could be improved upon by adding omega-3 fatty acids, lutein and zeaxanthin, as well as removing beta-carotene and/or reducing zinc. Observational studies have suggested that omega-3 fatty acids along with the carotenoids lutein and zeaxanthin may be associated with a decreased risk of developing advanced AMD. The placebo-controlled, randomized, double-blind portion of the AREDS2 study was conducted in 2006-2012 with 4203 participants enrolled who were aged 50-85 years. Participants enrolled in the AREDS2 study were at risk for progression to AMD with bilateral large drusen or a large drusen in one (1) eye and advanced AMD in the other eye. Participants were randomized to receive supplements containing ten (10) mg lutein and two (2) mg zeaxanthin or three hundred and fifty (350) mg DHA and six hundred and fifty (650) mg EPA or ten (10) mg lutein, two (2) mg zeaxanthin, three hundred and fifty (350) mg DHA and six hundred and fifty (650) mg EPA. All participants were also supplemented with the original AREDS formulation or a secondary randomization to variations of the AREDS formulation, including elimination of beta carotene, lowering the amount of zinc, or both. Age-Related Eye Disease Study 2 (AREDS2) Research Group. (2013). Lutein+Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. JAMA, 309(19): 2005-15.
The modified formulation in the AREDS2 study which contained omega-3 fatty acids or lutein and zeaxathin or both showed no statistically significant difference in risk reduction of AMD over the original AREDS formula. However, the AREDS2 study group did find that individuals low in dietary lutein and zeaxanthin were about 25% less likely to develop advanced AMD compared to participants with similar dietary intake who did not take lutein and zeaxanthin. The removal of beta-carotene did not affect the formulation's protective effect against developing AMD. The researchers found that formulations containing lutein and zeaxanthin and no beta-carotene had a reduction in developing advanced AMD by 18% compared to participants who took the AREDS2 formula with beta-carotene and no lutein or zeaxanthin. Beta-carotene was shown to compete with lutein and zeaxanthin as individuals who took all three nutrients had lower levels of circulating lutein and zeaxanthin when compared to participants who took lutein and zeaxanthin without beta-carotene. The AREDS2 study also showed lowering the amount of zinc had no effect on AMD progression but there was a positive association found between beta-carotene and the risk of lung cancer among former smokers. The AREDS2 clinical trial provides evidence that long-term use of AREDS supplements appears safe and protective against advanced AMD and the addition of lutein and zeaxanthin in place of beta-carotene further improves the original formulation.
U.S. Pat. No. 6,660,297 discloses retinal health supplements containing: approximately 7 to 10 times the RDA of vitamin C; approximately 13 to 18 times the RDA of vitamin E; approximately 6 to 10 times the RDA of vitamin A in the form of beta-carotene; approximately 4 to 7 times the RDA of Zinc; and at least 1.6 mg copper.
U.S. Pat. No. 7,267,830 claims dietary supplements for macular degeneration comprising approximately 0.03% to 0.3% copper (by weight), approximately 0.2% to 4% zinc (by weight), approximately 10% to 30% Vitamin C (by weight), and approximately 1.0% to 25% co-beadlets (by weight), wherein the cobeadlets comprise: approximately 0.5% to 25% Vitamin E (by weight), and approximately 10% to 30% (by weight) active carotenoid in the form of β-carotene and xanthophyll selected from the group consisting of lutein, zeaxanthin, and a mixture thereof. It also claims: dietary supplements further comprising: about 125 mg Vitamin C; about 0.4 mg copper; about 20 mg Zinc; and said co-beadlets, Which comprise: about 100 IU Vitamin E about 0.75 mg [3-carotene; about 11.25 mg lutein; and about 3.75 mg Zeaxanthin.
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